Glioma is the most common primary brain tumor.Exploration of new tumorigenesis mechanism of glioma is critical to determine more effective treatment targets as well as to develop effective prognosis methods that can e...Glioma is the most common primary brain tumor.Exploration of new tumorigenesis mechanism of glioma is critical to determine more effective treatment targets as well as to develop effective prognosis methods that can enhance the treatment efficacy.We previously demonstrated that the deubiquitinase biquitin carboxyl-terminal hydrolase L5(UCHL5)was downregulated in human glioma.However,the effect and mechanism of UCHL5 on the proliferation of glioma cells remains unknown.Methods:Transfection of siRNA was used to knockdown the expression of UCHL5 in U251 cells.The 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide(MTT)assay,Edu assay,and colony formation assay were employed to identify the effect of UCHL5 on the proliferation of U251 glioma cells.Western blotting and quantitative real-time PCR were carried out to detect the interaction of UCHL5 and PTEN.The effect of UCHL5 on the growth of glioma in vivo was evaluated in nude mice.Then Immunohistochemistry(IHC)were performed to analysis the expression of UCHL5 and PTEN in human glioma tissues.Results:Here,we have reported that silencing of UCHL5 could promote the proliferation of U251 glioma cells through MTT assay,Edu assay,and colony formation assay.Mechanically,we revealed that UCHL5 stabilizes the phosphatase and tensin homolog(PTEN)expression by deubiquitination,thereby inhibiting cell proliferation in U251 cells.Tumor xenograft experiments further demonstrated that silencing the UCHL5 expression could accelerate U251 cell growth in vivo.Finally,in human glioma tissue microarray,the positive correlation between UCHL5 and PTEN expression was confirmed through IHC assay.Conclusion:UCHL5 restrains the proliferation of U251 glioma cells by stabilizing and deubiquitinating PTEN.Our findings provide ideas for developing enhanced targeted PTEN therapy for patients with glioma.展开更多
In view of the composition analysis and identification of ancient glass products, L1 regularization, K-Means cluster analysis, elbow rule and other methods were comprehensively used to build logical regression, cluste...In view of the composition analysis and identification of ancient glass products, L1 regularization, K-Means cluster analysis, elbow rule and other methods were comprehensively used to build logical regression, cluster analysis, hyper-parameter test and other models, and SPSS, Python and other tools were used to obtain the classification rules of glass products under different fluxes, sub classification under different chemical compositions, hyper-parameter K value test and rationality analysis. Research can provide theoretical support for the protection and restoration of ancient glass relics.展开更多
Dear Editor,Liver cancer as a common malignant tumor has become a major source of morbidity and mortality worldwide.1 Currently,four synthetic drugs and three monoclonal antibody drugs have been approved for the treat...Dear Editor,Liver cancer as a common malignant tumor has become a major source of morbidity and mortality worldwide.1 Currently,four synthetic drugs and three monoclonal antibody drugs have been approved for the treatment of hepatocellular carcinoma(HCC)since 2007.Whereas,the disadvantages of the above drugs such as low response rates,severe side effects,and drug resistance hamper their therapeutic effects.Structurally and biologically diverse natural products are a major source in the search for novel antihepatoma agents.展开更多
Objective:To systematically evaluate the safety and efficacy of acupuncture on patients with postherpetic neuralgia.Methods:Based on the heyword retrieval method,China National Knowledge Infrastructure(CNKI,1978-2020)...Objective:To systematically evaluate the safety and efficacy of acupuncture on patients with postherpetic neuralgia.Methods:Based on the heyword retrieval method,China National Knowledge Infrastructure(CNKI,1978-2020),China Biomedical Literature database(CBM,1979-2020),VIP database(WEIPU,1989-2020),Wanfang database(1989-2020),Cochrane Library,PubMed,and Embase were searched;randomized controlled trials of the use of acupuncture in the treatment of postherpetic neuralgia were screened out;the quality of the included literatures was evaluated based on the evaluation criteria in the Cochrane Handbook,and meta-analysis was performed using RevMan 5.3.Results:Twenty-six literatures that met the criteria,involving 2,174 patients,were included;the meta-analysis showed that compared with western medicine,the use of acupuncture can improve the overall effective rate(RR=1.24,95%CI[1.17,1.32],P<0.00001)and reduce the VAS score(MD=-1.43,95%CI[-1.97,-0.89],P<0.00001).Conclusion:The use of acupuncture can further improve the clinical effect of patients with postherpetic neuralgia.展开更多
The development of promising strategies to improve the treatment efficacy of pancreatic carcinoma still remains to be a challenging task.We report here the development of a new dendrimer-based nanomedicine formulation...The development of promising strategies to improve the treatment efficacy of pancreatic carcinoma still remains to be a challenging task.We report here the development of a new dendrimer-based nanomedicine formulation to tackle pancreatic carcinoma through apoptosis-enhanced ferroptosis therapy.In this article,G5 dendrimers were partially modified with a Fe(Ⅲ)chelator hydroxyquinoline-2-carboxylic acid(8-HQC)on their periphery,entrapped with gold nanoparticles(Au NPs)within their internal cavities,and chelated with Fe(Ⅲ).The thus created dendrimer-entrapped Au NPs(Fe-Au DENP-HQC)with an Au core size of 1.9 nm and 20.0 Fe(Ⅲ)ions complexed per dendrimer are stable,have a pH-dependent Fe(Ⅲ)release profile,and can generate reactive oxygen species under the tumor microenvironment(TME)and effectively compact plasmid DNA encoding p53 protein to form polyplexes with a hydrodynamic size of 143.9 nm and a surface potential of 33.6 mV.We show that cancer cells treated with the created Fe-Au DENP-HQC/p53 polyplexes can be more significantly inhibited through vector-mediated chemodynamic therapy(CDT)effect via Fe(Ⅲ)-induced Fenton reaction and the p53 gene delivery-boosted cell apoptosis and oxidative stress in the TME than single-mode CDT and gene therapy.Further investigations using a xenografted tumor model validated the effectiveness of apoptosis-enhanced ferropotosis therapy through the downregulation of GPX-4 and SLC7A11proteins,upregulation of p53 and PTEN proteins,as well as histological examinations.Meanwhile,the dendrimer nanoplatform enabled tumor fluorescence imaging through gene delivery-mediated enhanced green fluorescent protein expression.The Fe(Ⅲ)-complexed dendrimer vector system may be developed as a promising theranostic nanoplatform for ferroptosis or ferroptosis-based combination therapy of other cancer types.展开更多
Root-associated microbes are critical for plant growth and nutrient acquisition. However, scant information exists on optimizing communities of beneficial root-associated microbes or the mechanisms underlying their in...Root-associated microbes are critical for plant growth and nutrient acquisition. However, scant information exists on optimizing communities of beneficial root-associated microbes or the mechanisms underlying their interactions with host plants. In this report, we demonstrate that rootassociated microbes are critical influencers of host plant growth and nutrient acquisition. Three synthetic communities(SynComs) were constructed based on functional screening of 1,893 microbial strains isolated from root-associated compartments of soybean plants. Functional assemblage of SynComs promoted significant plant growth and nutrient acquisition under both N/P nutrient deficiency and sufficiency conditions.Field trials further revealed that application of SynComs stably and significantly promoted plant growth, facilitated N and P acquisition, and subsequently increased soybean yield. Among the tested communities, SynCom1 exhibited the greatest promotion effect, with yield increases of up to 36.1% observed in two field sites. Further RNA-seq implied that SynCom application systemically regulates N and P signaling networks at the transcriptional level, which leads to increased representation of important growth pathways, especially those related to auxin responses. Overall,this study details a promising strategy for constructing SynComs based on functional screening,which are capable of enhancing nutrient acquisition and crop yield through the activities of beneficial root-associated microbes.展开更多
Summary of main observation and conclusion Stimuli-responsive hydrogels crosslinked by weak noncovalent bonds such as hydrogen bonds,ionic interactions,host-guest interactions and hydrophobic interactions have been ex...Summary of main observation and conclusion Stimuli-responsive hydrogels crosslinked by weak noncovalent bonds such as hydrogen bonds,ionic interactions,host-guest interactions and hydrophobic interactions have been extensively investigated.Herein,azobenzene and spiropyran acting as two hydrophobic pendant groups were introduced into a hydrophilic polyacrylamide (PAM) via free radical copolymerization to construct a hydrophobic interaction based thermo-,light-responsive polymer hydrogel.Its viscosity and color could be reversibly regulated by heating and cooling.Meanwhile,its color could be specifically switched by light without obvious viscosity change.The gel was also capable of being transited to sol by addition of β-cyclodextrin (β-CD),which encaged the hydrophobic groups and then increased the solubility of polymer in water.The hydrogel could be regained after UV irradiation at λ=365 nm,and after irradiation at λ=440 nm,the hydrogel changed into a clear sol again.展开更多
This paper proposed a novel distributed memetic evolutionary model,where four modules distributed exploration,intensified exploitation,knowledge transfer,and evolutionary restart are coevolved to maximize their streng...This paper proposed a novel distributed memetic evolutionary model,where four modules distributed exploration,intensified exploitation,knowledge transfer,and evolutionary restart are coevolved to maximize their strengths and achieve superior global optimality.Distributed exploration evolves three independent populations by heterogenous operators.Intensified exploitation evolves an external elite archive in parallel with exploration to balance global and local searches.Knowledge transfer is based on a point-ring communication topology to share successful experiences among distinct search agents.Evolutionary restart adopts an adaptive perturbation strategy to control search diversity reasonably.Quantum computation is a newly emerging technique,which has powerful computing power and parallelized ability.Therefore,this paper further fuses quantum mechanisms into the proposed evolutionary model to build a new evolutionary algorithm,referred to as quantum-inspired distributed memetic algorithm(QDMA).In QDMA,individuals are represented by the quantum characteristics and evolved by the quantum-inspired evolutionary optimizers in the quantum hyperspace.The QDMA integrates the superiorities of distributed,memetic,and quantum evolution.Computational experiments are carried out to evaluate the superior performance of QDMA.The results demonstrate the effectiveness of special designs and show that QDMA has greater superiority compared to the compared state-of-the-art algorithms based on Wilcoxon’s rank-sum test.The superiority is attributed not only to good cooperative coevolution of distributed memetic evolutionary model,but also to superior designs of each special component.展开更多
基金supported by grants from the Shenzhen Science and Technology Innovation Commission Grant(Nos.JCYJ20180507182253653 and JCYJ20190808172201639)Guangdong Province Basic and Applied Basic Research Fund(No.2022A1515111143).
文摘Glioma is the most common primary brain tumor.Exploration of new tumorigenesis mechanism of glioma is critical to determine more effective treatment targets as well as to develop effective prognosis methods that can enhance the treatment efficacy.We previously demonstrated that the deubiquitinase biquitin carboxyl-terminal hydrolase L5(UCHL5)was downregulated in human glioma.However,the effect and mechanism of UCHL5 on the proliferation of glioma cells remains unknown.Methods:Transfection of siRNA was used to knockdown the expression of UCHL5 in U251 cells.The 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide(MTT)assay,Edu assay,and colony formation assay were employed to identify the effect of UCHL5 on the proliferation of U251 glioma cells.Western blotting and quantitative real-time PCR were carried out to detect the interaction of UCHL5 and PTEN.The effect of UCHL5 on the growth of glioma in vivo was evaluated in nude mice.Then Immunohistochemistry(IHC)were performed to analysis the expression of UCHL5 and PTEN in human glioma tissues.Results:Here,we have reported that silencing of UCHL5 could promote the proliferation of U251 glioma cells through MTT assay,Edu assay,and colony formation assay.Mechanically,we revealed that UCHL5 stabilizes the phosphatase and tensin homolog(PTEN)expression by deubiquitination,thereby inhibiting cell proliferation in U251 cells.Tumor xenograft experiments further demonstrated that silencing the UCHL5 expression could accelerate U251 cell growth in vivo.Finally,in human glioma tissue microarray,the positive correlation between UCHL5 and PTEN expression was confirmed through IHC assay.Conclusion:UCHL5 restrains the proliferation of U251 glioma cells by stabilizing and deubiquitinating PTEN.Our findings provide ideas for developing enhanced targeted PTEN therapy for patients with glioma.
文摘In view of the composition analysis and identification of ancient glass products, L1 regularization, K-Means cluster analysis, elbow rule and other methods were comprehensively used to build logical regression, cluster analysis, hyper-parameter test and other models, and SPSS, Python and other tools were used to obtain the classification rules of glass products under different fluxes, sub classification under different chemical compositions, hyper-parameter K value test and rationality analysis. Research can provide theoretical support for the protection and restoration of ancient glass relics.
基金This work was financially supported by the Key Program of the National Natural Science Foundation of China(22137008)the Xingdian Yingcai Project(YNWR-KJLJ-2019-002)+4 种基金the Youth Fund Program of the National Natural Science Foundation of China(82104040)the Funded by CAS Special Research Assistant(E12D9211Q1)the Youth Innovation Promotion Association,CAS(2020386)the Reserve Talents of Young and Middle-aged Academic and Technical Leaders in Yunnan Province(202105AC160021)Postdoctoral Directional Training Foundation of Yunnan Province(E131821261).The authors are grateful to Prof.Jian Ding,Prof.Hongchun Liu,and Dr.Hui Xu(Shanghai Institute of Materia Medica,Chinese Academy of Sciences)for their kind help in cytotoxic assay against THLE-2 cells,to Ms.Yaomei He and Senior Engineer Lian Yang(Kunming Institute of Botany,Chinese Academy of Sciences)for their help in network pharmacology analysis and the isothermal titration calorimetry and Surface Plasmon Resonance assay.
文摘Dear Editor,Liver cancer as a common malignant tumor has become a major source of morbidity and mortality worldwide.1 Currently,four synthetic drugs and three monoclonal antibody drugs have been approved for the treatment of hepatocellular carcinoma(HCC)since 2007.Whereas,the disadvantages of the above drugs such as low response rates,severe side effects,and drug resistance hamper their therapeutic effects.Structurally and biologically diverse natural products are a major source in the search for novel antihepatoma agents.
文摘Objective:To systematically evaluate the safety and efficacy of acupuncture on patients with postherpetic neuralgia.Methods:Based on the heyword retrieval method,China National Knowledge Infrastructure(CNKI,1978-2020),China Biomedical Literature database(CBM,1979-2020),VIP database(WEIPU,1989-2020),Wanfang database(1989-2020),Cochrane Library,PubMed,and Embase were searched;randomized controlled trials of the use of acupuncture in the treatment of postherpetic neuralgia were screened out;the quality of the included literatures was evaluated based on the evaluation criteria in the Cochrane Handbook,and meta-analysis was performed using RevMan 5.3.Results:Twenty-six literatures that met the criteria,involving 2,174 patients,were included;the meta-analysis showed that compared with western medicine,the use of acupuncture can improve the overall effective rate(RR=1.24,95%CI[1.17,1.32],P<0.00001)and reduce the VAS score(MD=-1.43,95%CI[-1.97,-0.89],P<0.00001).Conclusion:The use of acupuncture can further improve the clinical effect of patients with postherpetic neuralgia.
基金supported by the National Natural Science Foundation of China(81761148028,21773026)the Science and Technology Commission of Shanghai Municipality(19XD1400100,20520710300,21490711500,20DZ2254900)the Shanghai Education Commission through the Shanghai Leading Talents Program。
文摘The development of promising strategies to improve the treatment efficacy of pancreatic carcinoma still remains to be a challenging task.We report here the development of a new dendrimer-based nanomedicine formulation to tackle pancreatic carcinoma through apoptosis-enhanced ferroptosis therapy.In this article,G5 dendrimers were partially modified with a Fe(Ⅲ)chelator hydroxyquinoline-2-carboxylic acid(8-HQC)on their periphery,entrapped with gold nanoparticles(Au NPs)within their internal cavities,and chelated with Fe(Ⅲ).The thus created dendrimer-entrapped Au NPs(Fe-Au DENP-HQC)with an Au core size of 1.9 nm and 20.0 Fe(Ⅲ)ions complexed per dendrimer are stable,have a pH-dependent Fe(Ⅲ)release profile,and can generate reactive oxygen species under the tumor microenvironment(TME)and effectively compact plasmid DNA encoding p53 protein to form polyplexes with a hydrodynamic size of 143.9 nm and a surface potential of 33.6 mV.We show that cancer cells treated with the created Fe-Au DENP-HQC/p53 polyplexes can be more significantly inhibited through vector-mediated chemodynamic therapy(CDT)effect via Fe(Ⅲ)-induced Fenton reaction and the p53 gene delivery-boosted cell apoptosis and oxidative stress in the TME than single-mode CDT and gene therapy.Further investigations using a xenografted tumor model validated the effectiveness of apoptosis-enhanced ferropotosis therapy through the downregulation of GPX-4 and SLC7A11proteins,upregulation of p53 and PTEN proteins,as well as histological examinations.Meanwhile,the dendrimer nanoplatform enabled tumor fluorescence imaging through gene delivery-mediated enhanced green fluorescent protein expression.The Fe(Ⅲ)-complexed dendrimer vector system may be developed as a promising theranostic nanoplatform for ferroptosis or ferroptosis-based combination therapy of other cancer types.
基金supported by the by National Natural Science Foundation of China(No.31830083)China National Key Program for Research and Development(No.2016YFD0100700)。
文摘Root-associated microbes are critical for plant growth and nutrient acquisition. However, scant information exists on optimizing communities of beneficial root-associated microbes or the mechanisms underlying their interactions with host plants. In this report, we demonstrate that rootassociated microbes are critical influencers of host plant growth and nutrient acquisition. Three synthetic communities(SynComs) were constructed based on functional screening of 1,893 microbial strains isolated from root-associated compartments of soybean plants. Functional assemblage of SynComs promoted significant plant growth and nutrient acquisition under both N/P nutrient deficiency and sufficiency conditions.Field trials further revealed that application of SynComs stably and significantly promoted plant growth, facilitated N and P acquisition, and subsequently increased soybean yield. Among the tested communities, SynCom1 exhibited the greatest promotion effect, with yield increases of up to 36.1% observed in two field sites. Further RNA-seq implied that SynCom application systemically regulates N and P signaling networks at the transcriptional level, which leads to increased representation of important growth pathways, especially those related to auxin responses. Overall,this study details a promising strategy for constructing SynComs based on functional screening,which are capable of enhancing nutrient acquisition and crop yield through the activities of beneficial root-associated microbes.
基金the National Natural Science Foundation of China (No.21402053)State Key Laboratory of Molecular Engineering of Polymers (Fudan University)(K2018-20) for financial support of this study.
文摘Summary of main observation and conclusion Stimuli-responsive hydrogels crosslinked by weak noncovalent bonds such as hydrogen bonds,ionic interactions,host-guest interactions and hydrophobic interactions have been extensively investigated.Herein,azobenzene and spiropyran acting as two hydrophobic pendant groups were introduced into a hydrophilic polyacrylamide (PAM) via free radical copolymerization to construct a hydrophobic interaction based thermo-,light-responsive polymer hydrogel.Its viscosity and color could be reversibly regulated by heating and cooling.Meanwhile,its color could be specifically switched by light without obvious viscosity change.The gel was also capable of being transited to sol by addition of β-cyclodextrin (β-CD),which encaged the hydrophobic groups and then increased the solubility of polymer in water.The hydrogel could be regained after UV irradiation at λ=365 nm,and after irradiation at λ=440 nm,the hydrogel changed into a clear sol again.
基金the National Natural Science Foundation of China(No.62273193)the Talent Introducing Project of Hebei Agricultural University(Nos.KY201903 and YJ201953).
文摘This paper proposed a novel distributed memetic evolutionary model,where four modules distributed exploration,intensified exploitation,knowledge transfer,and evolutionary restart are coevolved to maximize their strengths and achieve superior global optimality.Distributed exploration evolves three independent populations by heterogenous operators.Intensified exploitation evolves an external elite archive in parallel with exploration to balance global and local searches.Knowledge transfer is based on a point-ring communication topology to share successful experiences among distinct search agents.Evolutionary restart adopts an adaptive perturbation strategy to control search diversity reasonably.Quantum computation is a newly emerging technique,which has powerful computing power and parallelized ability.Therefore,this paper further fuses quantum mechanisms into the proposed evolutionary model to build a new evolutionary algorithm,referred to as quantum-inspired distributed memetic algorithm(QDMA).In QDMA,individuals are represented by the quantum characteristics and evolved by the quantum-inspired evolutionary optimizers in the quantum hyperspace.The QDMA integrates the superiorities of distributed,memetic,and quantum evolution.Computational experiments are carried out to evaluate the superior performance of QDMA.The results demonstrate the effectiveness of special designs and show that QDMA has greater superiority compared to the compared state-of-the-art algorithms based on Wilcoxon’s rank-sum test.The superiority is attributed not only to good cooperative coevolution of distributed memetic evolutionary model,but also to superior designs of each special component.
